1. Field of the Invention
This invention relates to pharmaceutical compositions, dosage forms and their use in the treatment of chronic disease. More particularly, it concerns pharmaceutical compositions and dosage forms and their use in the treatment of the pain and locomotor dysfunction of rheumatoid arthritis, and osteoarthritis.
2. Discussion of Prior Art
Rheumatoid arthritis is a serious, often crippling, disease characterized by pain and locomotor dysfunction. As pointed out by Nickander et al in their article "Nonsteroidal Antiinflammatory Agents" which appeared at Ann. Rev. Pharmacol. Toxicol., 1979, 19:469-90, this sort of pain and locomotor dysfunction are among man's most common and frustrating afflictions. The gravity of this disease has led to the investigation and/or adoption of a wide range of drugs for its alleviation. Aspirin has been commonly used since the turn of this century. Other major drugs for arthritis have historically included indomethacin, other salicylates, phenylbutazone, steroids and gold. While more recently, fenoprofen, ibuprofen, naproxen, sulindac and tolmetin have been approved for use in the United States.
While these compounds can offer antiinflammatory, antipyretic and analgesic effects and have proven helpful in the management of rheumatoid arthritis in many patients, when combined with other modalities such as proper rest, exercise, physical therapy and surgery, they are less than ideal. Many exhibit serious side effects with many patients, particularly gastrointestinal damage and renal toxicity. Each of these materials have the failing of being far from universal--some patients will respond to one material while others respond favorably only to others.
Osteoarthritis is classified as a degenerative joint disease (Cecil-Loeb TEXTBOOK OF MEDICINE, 13th Edition, W. B. Saunders Co., Beeson and McDermott Editors). This painful disease is similar in many respects to rheumatoid arthritis in its symptoms and effects on the patient's well being. Salicylates, such as aspirin, phenylbutazone, and other analgesics and antiflammatory agents, have been used in the prior art to alleviate the symptoms of osteoarthritis.
Cocaine and cocaine free base have been employed in the management of rheumatoid arthritis for a number of years. I have demonstrated, through clinical experiments on a range of patients suffering from rheumatoid arthritis, the effectiveness of this treatment.
Unfortunately for this possible therapeutic use, cocaine and cocaine free base are widely regarded as materials of abuse. It is most unlikely that the regulatory and drug enforcement agency issues will ever be resolved to a point that cocaine or its free base can be available on as widespread a basis as would be required for their use in the treatment of sufferers of rheumatoid arthritis. In addition, certain individuals can develop dependence upon these materials and/or exhibit symptoms of intoxication when using them.
The metabolic pathway for the degradation of the alkaloid cocaine in experimental animals and man has been extensively studied. Moreover, numerous synthetic analogs and derivatives of the alkaloid have been made. The following articles, publications and patents are examples of the vast scientific literature related to cocaine, its metabolites and derivatives: Disposition of [.sup.3 H] benzoylnorecgonine (Cocaine Metabolite) in the Rat, by A. L. Misra, et al., Research Communications in Chemical Pathology and Pharmacology, Volume 13, pages 579-584 (1976); Physiologic Distribution and Metobolism of [.sup.3 H] Ecgonine (Cocaine Metobolite) in the Rat, by A. L. Misra, et al., Research Communications in Chemical Pathology and Pharmacology, Volume 8, pages 55-63 (1974); Excretion of Cocaine and its Metobolites in Man, by F. Fish, et al., J. Pharm. Pharmac., 21 Suppl., 135S-138S (1969); U.S. Pat. Nos. 2,948,730 and 2,893,966.
In addition to the investigative studies which shed light on the metabolic fate of the therapeutically effective but dangerous substance cocaine, what is needed even more in the healing arts is effective treatment of rheumatoid arthritis and osteoarthritis by derivatives of cocaine which, however, have no significant potential for abuse. More specifically, what is needed is a pharmaceutical preparation and/or dosage form and a method for its use that does not involve cocaine or its free base, that does not present the untoward physiological effects of cocaine but which acts therapeutically in the manner of cocaine to alleviate the pain and motor dysfunction of rheumatoid arthritis and of osteoarthritis.